Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change.
Genetic variations in apolipoprotein E (APOE) and proximal genes (PVRL2, TOMM40, and APOC1) are associated with cognitive function and dementia, particularly Alzheimer's disease.
Both methods' results showed two identical significant SNPs associated with the A β-42 levels in CSF (rs2075650 at intron region TOMM40 with p-value ≥ 1 × 10-16 and rs439401 in the intergenic region of LOC100129500 and APOC1 with p-value ≥ 1 × 10-9) and highlighted APOC1 and TOMM40, which are well-known genes previously associated with AD.
The haplotypes E*3/-317*ins and E*4/-317*ins of APOE/APOC1 genes were significantly more frequent in the groups with Alzheimer's disease and dementia in general (P < 0.001).
In conclusion, human apoC-I expression impairs cognitive functions in mice independent of apoE expression, which supports the potential of a modulatory role for apoC-I during the development of AD.
In conclusion, human apoC-I expression impairs cognitive functions in mice independent of apoE expression, which supports the potential of a modulatory role for apoC-I during the development of AD.
In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk.